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Wipf, P.; Pierce, J. G. Org. Lett. 2005, 7, 3537 For a recent example using in situ generated allylic titanium reagents, see: Gao, Y.; Sato, F. J. Org. Chem. 1995, 60, 8136 For reviews on the synthesis of homoallylic amines via allylic metal reagents, see: Ramachandran, P. V.; Burghardt, T. E. Pure Appl. Chem. 2006, 78, 1397
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73
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0001089557
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For a rare example of imine prenylation, see
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For a rare example of imine prenylation, see: Yanagisawa, A.; Ogasawara, K.; Yasue, K.; Yamamoto, H. J. Chem. Soc., Chem. Commun. 1996, 367
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75
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0034755306
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Few reactions are broadly useful for the formation of homoallylic amines that establish both an allylic stereocenter and a stereodefined alkene. Examples include
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Few reactions are broadly useful for the formation of homoallylic amines that establish both an allylic stereocenter and a stereodefined alkene. Examples include: Kazmaier, U.; Zumpe, F. L. Eur. J. Org. Chem. 2001, 4067
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Garigipati, R. S.; Cordova, R.; Parvez, M.; Weinreb, S. M. Tetrahedron 1986, 42, 2979
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80
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41849126809
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For a recent evaluation of the rate of interconversion of zirconaaziridine enantiomers, see
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For a recent evaluation of the rate of interconversion of zirconaaziridine enantiomers, see: Cummings, S. A.; Tunge, J. A.; Norton, J. R. J. Am. Chem. Soc. 2008, 130, 4669
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78650258024
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these experiments, 2 equiv of the imine were employed. While it is likely that the chiral Ti-imine complex rapidly undergoes inversion, these experiments cannot provide support that the current process defines a dynamic kinetic resolution
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In these experiments, 2 equiv of the imine were employed. While it is likely that the chiral Ti-imine complex rapidly undergoes inversion, these experiments cannot provide support that the current process defines a dynamic kinetic resolution.
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83
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78650256811
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Note that the %ee of homoallylic amine products (eqs 12-14) reflect the %ee of the allylic alcohol starting materials. While we were also successful at accomplishing asymmetric coupling between a chiral allylic alcohol possessing a trisubstituted alkene [(R)- 34 ] and imine 14, we were unable to establish the ee of the homoallylic amine product by HPLC or derivatization (this coupling reaction proceeded in 77% yield). Given the likely mechanistic course of this coupling reaction, and our inability to identify a minor isomer, the transfer of stereochemical information in this process is reasoned to be as high as that depicted in eq 12. This expectation is in accord with a the highly diastereoselective coupling of imine 14 with the chiral allylic alcohol 60 which occurred with superb levels of diastereoselectivity. (10a)
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Note that the %ee of homoallylic amine products (eqs 12-14) reflect the %ee of the allylic alcohol starting materials. While we were also successful at accomplishing asymmetric coupling between a chiral allylic alcohol possessing a trisubstituted alkene [(R)- 34 ] and imine 14, we were unable to establish the ee of the homoallylic amine product by HPLC or derivatization (this coupling reaction proceeded in 77% yield). Given the likely mechanistic course of this coupling reaction, and our inability to identify a minor isomer, the transfer of stereochemical information in this process is reasoned to be as high as that depicted in eq 12. This expectation is in accord with a the highly diastereoselective coupling of imine 14 with the chiral allylic alcohol 60 which occurred with superb levels of diastereoselectivity. (10a)
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84
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72449190565
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During the course of these studies with allylsilanes, we observed that a simple allylsilane related to 73, but bearing a primarly allylic alcohol, undergoes reductive cross-coupling with aromatic imines in a uniquely regioselective manner. Here, C-C bond formation occurs primarily at the internal carbon of the alkene, generating a 1,3-aminoalcohol product. Studies aimed at understanding this shift in site-selectivity are ongoing
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Yang, D.; Micalizio, G. C. J. Am. Chem. Soc. 2009, 131, 17548. During the course of these studies with allylsilanes, we observed that a simple allylsilane related to 73, but bearing a primarly allylic alcohol, undergoes reductive cross-coupling with aromatic imines in a uniquely regioselective manner. Here, C-C bond formation occurs primarily at the internal carbon of the alkene, generating a 1,3-aminoalcohol product. Studies aimed at understanding this shift in site-selectivity are ongoing.
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78650267815
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For a discussion in the context of regioselective reductive cross-coupling reactions of disubstituted alkynes, see ref 17
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For a discussion in the context of regioselective reductive cross-coupling reactions of disubstituted alkynes, see ref 17.
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